The anticancer mechanism of a wasp venom peptide

Research from the group of Dr Paul Beales has provided mechanistic insight into why a wasp venom peptide has anticancer properties.

The MP1 peptide, found in the venom of the aggressive Brazilian social wasp Polybia Paulista, is known to be able to inhibit the proliferation of, and in some cases kill, a variety of cancer cells without harming healthy cells such as red blood cells. However, until now, it was unclear why the peptide has these properties.

The natural role of this peptide is as an antibiotic, which attacks microbial membranes due to their different molecular composition compared to the wasp’s own cells. The team hypothesized that pathological changes in membrane composition were responsible for this peptide’s ability to specifically target cancer cells. It is known that PE and PS lipids, which are normally “hidden” on the inner leaflet of cell membranes become exposed to the outer membrane leaflet in many cancer cells.

In collaboration with Sao Paulo State University in Brazil and Dr Simon Connell in the School of Physics and Astronomy, this hypothesis was tested on model lipid membranes that were mainly composed of PC lipids (the major component of cell membranes) and containing neither, one of, or both PE and PS lipids. A variety of advanced biophysical spectroscopy and imaging techniques were applied to study the MP1 peptide’s interaction with these membranes. It was found that the PS lipid is required to increase the concentration of bound peptide on the membrane, whereas the PE lipid significantly increases the membrane’s susceptibility to disruption by the peptide. This facilitates the formation of large holes across the membrane that would allow vital biochemical constituents to leak from the cell and would lead to the loss of transmembrane chemical gradients. Therefore changes in the membrane composition of cancer cells form a mechanistic basis for the anticancer properties of MP1.

This is early stage, fundamental research but these findings could in future aid the development of novel chemotherapies that target changes in the membrane composition of cancer cells. This would be a novel mechanism for an anticancer drug and so be particularly useful for the development of combination therapies where multiple drugs are used simultaneously to attack different parts of cancerous cells. The MP1 peptide has evolved as a natural antibiotic and not as an anticancer agent. Therefore it could be possible, now that there is insight into its mechanism of action, to improve the selectivity and potency of this peptide to cancer cells by designing modifications within its chemical structure.